我们在此描述了一名52岁的男性患者发烧的情况,关节炎,2013年出现中性粒细胞性皮肤病,随后出现了接受大剂量糖皮质激素治疗的巨噬细胞活化综合征.由于使用氨苯砜的几种免疫调节和免疫抑制(IS)药物疗法难以治疗的持续症状,甲氨蝶呤,他克莫司,英夫利昔单抗(IFX),和托珠单抗(TCZ),患者接受泼尼松龙(PSL)≥20mg/天抑制疾病活动.2017年,爱泼斯坦-巴尔病毒(EBV)相关的噬血细胞性淋巴组织细胞增生症(HLH)被诊断并最初接受由地塞米松组成的免疫化疗治疗,环孢菌素(CyA),和依托泊苷(ET)。由于对初始治疗的反应欠佳,由CHOP组成的细胞减少疗法(由环磷酰胺组成的联合化疗,阿霉素,长春新碱,和PSL)。该方案改善了EBV相关的HLH。稍后,使用甲泼尼龙1mg/天和CyA100mg/天,患者病情稳定。2022年,使用外周血白细胞Sanger测序的泛素化起始E1酶(UBA1)变异分析检测到先前报道的体细胞变异(NM_003334.3:c.118-1G>C),确认空泡的诊断,E1酶,X-linked,自身炎症,躯体(VEXAS)综合征。本病例的临床过程表明CHOP可能是VEXAS综合征的潜在治疗选择。在病理生理学中,具有UBA1变体的克隆扩增似乎起着关键作用。
We herein describe the
case of a 52-year-old male patient who presented with fever, arthritis, and neutrophilic dermatosis in 2013 and subsequently experienced macrophage activation syndrome treated with high-dose glucocorticoid therapy. Due to the persistent symptoms refractory to several immunomodulatory and immunosuppressive (IS) drug therapies with dapsone, methotrexate, tacrolimus, infliximab (IFX), and tocilizumab (TCZ), he received prednisolone (PSL) ≥20 mg/day to suppress disease activity. In 2017, Epstein-Barr virus (EBV)-associated haemophagocytic lymphohistiocytosis (HLH) was diagnosed and initially treated with immunochemotherapy consisting of dexamethasone, cyclosporine (CyA), and etoposide (ET). Because of the suboptimal response to the initial therapy, cytoreduction therapy consisting of
CHOP (combination chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and PSL) was administered. This regimen improved the EBV-associated HLH. Later, the patient\'s condition stabilised with methylprednisolone 1 mg/day and CyA 100 mg/day. In 2022, ubiquitylation-initiating E1 enzyme (UBA1) variant analysis using Sanger sequencing of peripheral blood leukocytes detected a previously reported somatic variant (NM_003334.3: c.118-1G>C), confirming the diagnosis of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. The clinical course in the present
case suggested the possibility that
CHOP could be a potential treatment option for VEXAS syndrome, in the pathophysiology of which the expansion of clones with UBA1 variant seems to play a pivotal role.